We propose to establish and build the COBRE Center for the Computational Biology of Human Disease at Brown University and affiliated hospitals. The motivation for this effort lies in the joint promise that personalized genomic medicine and novel analyses of Big Data are key elements in the identification and treatment of human disease. Sequencing a genome, a transcriptome, or even 100 of them is a routine procedure available to most researchers. However, converting these raw data into meaningful information is the new challenge generated by the progress in genomics. The underlying principle of this Center is that close collaboration between empirical and computational biologists with common challenges in the analysis of large data sets can accelerate the implementation of translational medicine. The Brown University Biomedical community is an ideal environment to achieve this goal. The close collaboration among Departments and the hospitals associated with the Warren Alpert Medical School provide the context for unifying biological and quantitative approaches to human disease. We will evolve a culture where computational and biological research is distributed within each research group. We propose an innovative joint mentoring strategy where each junior faculty member is advised by both computational and biological or clinical senior faculty members. Moreover, we will build a Core of biomedical Big Data scientists who build analysis tools common to multiple junior PIs, and collaborate directly with individual research teams. The long-term goal of the Center is to establish and grow a nexus of computational biology infrastructure for the greater Brown and hospital environments that will benefit all of Rhode Island. The objective of this proposal is to establish the infrastructure of the COBRE Center to support the research activities of Junior Investigators to ensure their transition to stand-alone R01-funded scientists. There are two Specific Aims related to the establishment of the Center, and five Research Projects spanning computational and clinical studies. Aim 1: Build the Administrative Core that will support the COBRE Center; Aim 2: Build the Biomedical Big Data Core that will support the research of Junior Investigators; Aim 3 individual research projects - Project 1: Incorporating Ethnic and Gender Disparities in Genomic Studies of Disease; Project 2: Integrative Genomics of Cancer Survival; Project 3: Tolerance of Viral/Bacterial Co-infections; Project 4: A Drug Repositioning Strategy for Healthspan Extension; Project 5: Computational Genomics of Preeclampsia.